Efficacy of neoadjuvant combination immune checkpoint inhibitor therapy in patients with resectable high grade melanomas: A systematic review and meta analysis of randomised control trials.

Abstract

e21512 Background: The standard treatment for resectable, macroscopic stage 3 melanoma is Surgery followed by adjuvant therapy but neoadjuvant combination immune checkpoint inhibitor(ICI) therapy has shown to significantly increase the survival of patients. This proportional systematic review and metaanalysis aims to evaluate efficacy of Neoadjuvant Combination ICI therapy in patients with resectable high grade Melanomas. Methods: A systematic literature search was done by searching PubMed,Embase and Cochrane for randomized controlled trials investigating Combination ICI in patients with high grade resectable melanomas published till January 2025.The primary endpoint was Complete pathological response(pCR) and secondary endpoints were near complete pathological response(pnCR) and major pathological response(mPR).Statistical analysis was carried out using R version 4.2.2.RAW(UNTRANSFORMED) proportion was used as an effect measure.Heterogeneity was examined with I2 statistics. Results: A total of 6 randomized controlled trials were included encompassing a total of 590 patients.The pooled proportion for pCR was 47.86% (95% CI: 41.83% to 53.90%), indicating that nearly half of the patients achieved a complete pathological response. No heterogeneity was observed (I² = 0%,Tau² = 0, Chi² = 2.31, df = 3, p = 0.51) reflective of high consistency in the included studies. Subgroup analysis comparing Ipilimumab and Nivolumab vs Relatlimab and Nivolumab showed no significant differences (Chi² = 1.56, df = 1, p = 0.21). Therefore suggesting that both combinations are similarly effective in achieving pCR in this patient population. The pooled proportion for pnCR was 11.13% (95% CI: 4.83% to 17.43%), with mild-to-moderate heterogeneity observed (I² = 31%, p = 0.24). Subgroup analysis revealed no statistically significant differences between Ipilimumab and Nivolumab versus Relatlimab and Nivolumab (Chi² = 0.95, df = 1, p = 0.33). While pnCR represents a smaller proportion of patients, it may still reflect meaningful tumor reduction in those not achieving pCR. The mPR rate was 60.07% (95% CI: 54.00% to 66.13%) demonstrating that the majority of patients derived benefit from neoadjuvant chemotherapy. No heterogeneity was observed (I² = 0%, Tau² = 0, Chi² = 0.66, df = 2, p = 0.72) and no significant differences were found between subgroups (Chi² = 0.43, df = 1, p = 0.51). Conclusions: This meta analysis highlights the potential of neoadjuvant chemotherapy as an effective strategy for patients with high grade resectable melanomas.Our results demonstrate that both Ipilimumab and Nivolumab and Relatlimab and Nivolumab regimens are equally effective, providing clinicians with flexibility in treatment selection based on patient-specific factors. RCTs with more sample size are needed to arrive at more definite conclusions.